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000308891 1001_ $$aTrailin, Andriy$$b0
000308891 245__ $$aSpatial Profiling and Prognostic Role of Tumor-Infiltrating CD8+ T and CD20+ B Cells in Metastatic Clear Cell Renal Cell Carcinoma Treated with Sequential Tyrosine Kinase Inhibitors and Nivolumab.
000308891 260__ $$aWyoming, NSW$$bIvyspring Internat. Publ.$$c2026
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000308891 520__ $$aBackground: Tumor-infiltrating lymphocytes (TILs) are known to influence disease progression and treatment response in clear cell renal cell carcinoma. This study aimed at evaluating the prognostic and predictive relevance of T and B cell infiltration patterns in patients with metastatic clear cell renal cell carcinoma (mRCC-cc) treated sequentially with tyrosine kinase inhibitors (TKIs) and the immune checkpoint inhibitor nivolumab. Methods: In this retrospective cohort study, immune cell densities (CD3+, CD8+ T cells and CD20+ B cells) were analyzed by immunohistochemistry and quantified using digital image analysis software QuPath in distinct tumor regions of primary tumor: tumor center (TC), inner margin (IM), outer margin (OM), and peritumoral (PT) region. Samples were obtained from 36 patients with mRCC-cc treated with TKIs in the first line and sequentially with nivolumab in the second or third-line setting. Associations between immune cell densities, clinicopathological features, and survival outcomes were assessed using univariable and multivariable Cox regression models. Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) were evaluated. Results: Densities of all immune cells were significantly higher in the OM and PT regions than in the TC and IM. Older age correlated with lower CD8+ T cell and CD20+ B cell densities, whereas higher tumor grade was associated with increased CD20+ B cell infiltration in IM. High CD20+ B cell density in IM and OM was significantly associated with shorter PFS during first-line TKI therapy (hazard ratio (HR) = 3.30, P = 0.015 and HR = 3.25, P = 0.016, respectively). In contrast, an intermediate CD8+ T cell density in the PT region was associated with longer PFS during sequential nivolumab treatment (HR = 0.26, P = 0.007). No significant associations between immune cell densities and ORR or OS were observed. Conclusions: Our findings suggest that spatial localization and density of tumor-infiltrating CD20+ B cells are potential predictors of poor PFS on TKIs, whereas higher CD8+ T cell infiltration in peritumoral areas may be a potential predictor of prolonged PFS on nivolumab. These immune-cell-based parameters may refine prognostic models and help guide treatment selection in mRCC-cc.
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000308891 650_7 $$2Other$$aimmune checkpoint inhibitors
000308891 650_7 $$2Other$$ametastatic renal cell carcinoma
000308891 650_7 $$2Other$$aprogression-free survival
000308891 650_7 $$2Other$$atumor-infiltrating lymphocytes
000308891 650_7 $$2Other$$atyrosine kinase inhibitors
000308891 7001_ $$aČervenková, Lenka$$b1
000308891 7001_ $$aHošek, Petr$$b2
000308891 7001_ $$aPivovarčíková, Kristýna$$b3
000308891 7001_ $$aTkadlecová, Michaela$$b4
000308891 7001_ $$aStránský, Petr$$b5
000308891 7001_ $$0P:(DE-He78)19b0ec1cea271419d9fa8680e6ed6865$$aHemminki, Kari$$b6$$udkfz
000308891 7001_ $$aFiala, Ondřej$$b7
000308891 773__ $$0PERI:(DE-600)2573318-7$$a10.7150/jca.125509$$gVol. 17, no. 2, p. 372 - 381$$n2$$p372 - 381$$tJournal of cancer$$v17$$x1837-9664$$y2026
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